1,5-Dibromo-2,4-difluorobenzene → (+/-)-1-(5-Bromo-2,4-difluorophenyl)-2-(but-3-en-2-yloxy)ethanone

Participants

Reaction Conditions

Reaction Steps

1,5-Dibromo-2,4-difluorobenzene (1.16 g, 4.28 mmol) was dissolved in Et2O (2 mL) and the solution was cooled to −78° C. nBuLi (1.26 mL 2.5M solution in hexanes) was added dropwise, maintaining the internal temperature below −70° C. Immediately after addition of nBuLi is complete, a solution of (±)-2-(but-3-en-2-yloxy)-N-methoxy-N-methylacetamide (0.5 g, 2.85 mmol) in Et2O (2 mL) was added dropwise, keeping the internal temperature below −70° C. The reaction was stirred at −78° C. for 15 minutes before quenching with saturated NH4Cl. The mixture was extracted with DCM (×3), dried (MgSO4) and concentrated in vacuo. The reaction was repeated a further 5 times on the same scale. The residues from all six reactions were combined and purified by column chromatography (Biotage SNAP 25 g 0-10% EtOAc in hexane) to leave the desired compound as a yellow oil (2 g). 1H NMR (400 MHz, CDCl3) δ ppm: 8.20 (t, J=7.46 Hz, 1H), 6.98 (dd, J=7.95, 10.15 Hz, 1H), 5.76 (ddd, J=7.70, 10.09, 17.42 Hz, 1H), 5.16-5.26 (m, 2H), 4.51-4.69 (m, 2H), 3.93-4.04 (m, 1H), 1.34-1.40 (m, 3H)

Provenance & Evidence